CEPHALOSPORINS

ANTIBIOTICS

Cephalosporins are the most frequently prescribed class of antibiotics

They are structurally and pharmacologically related to penicillins

Like penicillins, cephalosporins have a beta-lactam ring structure that interferes with the synthesis of bacterial cell wall

INTRODUCTION

Cephalosporins were first isolated from cultures of Cephalosporium acremonium from a sewer in 1948 by Italian scientist, Giuseppe Brotzu

The first agent cephalothin (cefalotin) was launched by Eli Lilly in 1964

Cephalosporins are derived from cephalosporin C which is an acid-stable molecule with antibacterial activity and is produced from Cephalosporium acremonium

Introduction cont..

The site of action of beta-lactam antibiotics is the penicillin binding proteins (PBPs) on the inner surface of the bacterial cell membrane that are involved in the synthesis of the cell wall

Mode of action cont..

Cephalosporins are bactericidal agents

All bacterial cells have a cell wall that protects them. Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls, which causes the walls to break down and eventually the bacteria die.

Mode of action cont..

First generation cephalosporins are predominantly active against gram-positive bacteria, and successive generations have increased activity against gram-negative bacteria

Cephalosporins are indicated for the treatment of bacterial infections caused by susceptible organisms

Indications

Cephalosporins are used to treat a wide variety of bacterial infections, such as

respiratory tract infections (pneumonia, tonsillitis, bronchitis),

skin infections and urinary tract infections. They are also commonly used for surgical

prophylaxis - prevention of bacterial infection before, during, and after surgery.

They are sometimes given with other antibiotics to increase the spectrum of activity

Indications cont...

Cephalosporins are grouped into "generations" based on their spectrum of antimicrobial activity.

The first cephalosporins were designated first generation while later, more extended spectrum cephalosporins were classified as second generation cephalosporins

Classification

Each newer generation of cephalosporins has significantly greater gram-negative antimicrobial properties than the preceding generation

Fourth generation cephalosporins, however, have true broad spectrum activity

Classification cont...

First generation cephalosporins are moderate spectrum agents

Effective against gram +ve aerobesThey are effective for treating staphylococcal

and streptococcal infections and therefore are alternatives for skin and soft-tissue infections, as well as for streptococcal pharyngitis.

1st generation cepahlosporins

Cefadroxil Cephalexin Cephaloridine Cephalothin Cephapirin Cefazolin Cephradine

The 1st generation cephalosporins are:

Their antibacterial spectrum is broader than that of 1st generation cephalosporins and includes some gram -ve pathogens

They are also more resistant to beta-lactamase

They are useful agents for treating upper and lower respiratory tract infections and sinusitis

2nd generation cephalosporins

These agents are also active against E. coli, Klebsiella and Proteus, which makes them potential alternatives for treating urinary tract infections caused by these organisms

The second generation cephalosporins are:Cefaclor, Cefoxitin, Cefprozil and Cefuroxime

2nd generation cont...

They have an extended spectrum of action against gram -ve organisms

Resistant to beta-lactamasesCeftiofur is used in the treatment of

respiratory disease in cattle, horses, sheep, and swine following IM injection and for intramammary treatment of mastitis in cattle

3rd generation cephalosporins

The parenteral third generation cephalosporins (ceftriaxone and cefotaxime) have excellent activity against most strains of Streptococcus pneumoniae, including the vast majority of those with intermediate and high level resistance to penicillin

The third generation cephalosporins are:Cefdinir , Cefixime, Cefpodoxime ,

Ceftibuten , Ceftriaxone , Cefotaxime

3rd generation cont...

4th generation cephalosporins are extended spectrum agents with similar activity against gram-positive organisms as first generation cephalosporins.

They also have a greater resistance to beta-lactamases than the third generation cephalosporins.

Many can cross blood brain barrier and are effective in meningitis.

4th generation cephalosporins

The fourth generation cephalosporins are:Cefepime Cefluprenam Cefozopran Cefpirome Cefquinome

4th generation cont...

They are organic acids and are hydrophilic They generally have poor oral bioavailability

as they unstable in acid environmentsThey are readily excreted by the kidneys, via

tubular secretion in the proximal convoluted tubule. This results in high concentrations of the drug in urine.

Pharmacokinetic consideration

Exceptions are: Cefalexin which is stable in acid and so

suitable for oral dosing. Ceforperazone is excreted in bile rather than

in urine.

Pharmacokinetic considerations cont..

Cephalosporins are considered to be among the safest antimicrobials in use.

Prolonged treatment/high doses may produce hemopoetic effects with anaemia and bone marrow depression

Hypersensitivity and allergic reactions may occur

Side Effects and Contraindications

They are often painful when given intramuscularly.

Very high doses has been known to result in nephrotoxicity.

They can result in bleeding problems because of interference with the formation of vitamin K in the gut.

Side effects cont...